Cystic fibrosis (CF) is a genetic disorder caused by a mutation in the gene that makes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. A specific type of mutation called a nonsense (premature stop codon) mutation is the cause of CF in approximately 10% of subjects with the disease.

Ataluren (PTC 124) is an orally delivered investigational drug that has the potential to overcome the effects of the nonsense mutation. This study was a Phase 3 trial that evaluated the clinical benefit of Ataluren (PTC124) in adult and pediatric patients with CF due to a nonsense mutation.

The main goals of the study were to understand whether Ataluren (PTC 124) can improve pulmonary function and whether the drug can safely be given for a long period of time. The study also assessed the effects of Ataluren (PTC 124) on CF pulmonary exacerbation frequency, cough frequency, health-related quality of life, antibiotic use for CF-related infections, CF-related disruptions to daily living, body weight, and CF pathophysiology.

ELIGIBILITY

Age:

>= 6 Years

FEV1:

40 - 90 Percent Predicted

P. aeruginosa status:

Not applicable

B. cepacia status:

Not applicable

Other Primary Eligibility Requirements:

To be included in this study patients are required to have documentation of the simultaneous presence of a nonsense mutation in at least 1 allele of the CFTR gene and a CF-causing mutation in the other CFTR allele, as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), or under the Clinical Laboratory Improvement Act/Amendment (CLIA), or by an equivalent organization.

Note: Detailed eligibility criteria information may be available on clinicaltrials.gov. If a specific
trial listing for this trial is available, a link to the specific clinicaltrials.gov listing will be present in the "More Information" section below.

Two hundred thirty-eight subjects age 6 years and older with nonsense mutation CF were enrolled in this multi-national, Phase 3 study to evaluate safety and efficacy of ataluren. Subjects received either 3 times daily ataluren (10 mg/kg morning and midday and 20 mg/kg evening) or placebo during the 48-week study. The primary endpoint, the relative change from baseline in %-predicted FEV1 at 48 weeks showed a positive trend favoring ataluren versus placebo that did not reach statistical significance.

Secondary Efficacy:

The secondary endpoint, the rate of pulmonary exacerbations did not reach statistical significance.

Safety:

Ataluren was generally well tolerated with incidence of adverse events similar in both groups through Week 48 except for cases of reversible Grade 3-4 creatinine elevations, associated with the combination of nephrotoxic antibiotics with ataluren.

The summary of data provided here is from a poster presented at the Cystic Fibrosis Foundation North American CF Conference (2012). These data may be preliminary and have not been peer-reviewed.